Familial multiple cavernous malformation syndrome
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The familial multiple cavernous malformation syndrome, or familial cerebral cavernous malformation syndrome, is uncommon, accounting for only a minority of cavernous malformations.
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It has been more frequently reported in patients of Hispanic descent 1.
The definition of familial multiple cavernous malformation syndrome is when there is one or more of the following 4,5:
multiple cerebral cavernous malformations
five or more cavernomas, or
one cavernoma and at least one other family member with one or more cavernomas
mutations in one of the three genes, KRIT1, CCM2 or PDCD10, which are associated with this disease
The presentation is most commonly with seizures (38-55%) 1 and focal neurological deficits, whilst recurrent large hemorrhages and headaches are less frequently encountered.
Cutaneous lesions, including cherry hemangiomas and café au lait spots, are occasionally associated 6.
In sporadic cases up to a 3rd of cavernous malformations are multiple. When familial the number of cavernomas is higher, typically five or more 1 and may be as high as dozens and dozens.
Familial cases usually have an autosomal dominant pattern of inheritance with incomplete penetrance 1,2.
See: Zabramski classification of cerebral cavernomas.
The radiographic appearance of each cavernous malformation depends on size although in many instances individuals have innumerable lesions randomly distributed throughout the brain.
For a discussion of the radiographic appearances see: cavernous malformations.
The differential is that of other causes of cerebral microhemorrhages, including 2:
cerebral amyloid angiopathy: usually numerous small foci
chronic hypertensive encephalopathy: more common in the basal ganglia
MRI appearance may be mimicked by:
artificial heart valve metallic emboli (very rare)
pneumocephalus (very rare) 3
- 1. Brunereau L, Labauge P, Tournier-Lasserve E, Laberge S, Levy C, Houtteville J. Familial Form of Intracranial Cavernous Angioma: MR Imaging Findings in 51 Families. French Society of Neurosurgery. Radiology. 2000;214(1):209-16. doi:10.1148/radiology.214.1.r00ja19209 - Pubmed
- 2. Jain R, Robertson P, Gandhi D, Gujar S, Muraszko K, Gebarski S. Radiation-Induced Cavernomas of the Brain. AJNR Am J Neuroradiol. 2005;26(5):1158-62. PMC8158583 - Pubmed
- 3. Palma J, Zubieta J, Dominguez P, Garcia-Eulate R. Pneumocephalus Mimicking Cerebral Cavernous Malformations in MR Susceptibility-Weighted Imaging. AJNR Am J Neuroradiol. 2009;30(6):e83; author reply e84. doi:10.3174/ajnr.A1549 - Pubmed
- 4. Rosário Marques I, Antunes F, Ferreira N, Grunho M. Familial Cerebral Cavernous Malformation: Report of a Novel KRIT1 Mutation in a Portuguese Family. Seizure. 2017;53:72-4. doi:10.1016/j.seizure.2017.10.020 - Pubmed
- 5. Mespreuve M, Vanhoenacker F, Lemmerling M. Familial Multiple Cavernous Malformation Syndrome: MR Features in This Uncommon but Silent Threat. J Belg Soc Radiol. 2016;100(1):51. doi:10.5334/jbr-btr.938 - Pubmed
- 6. Clatterbuck R & Rigamonti D. Cherry Angiomas Associated with Familial Cerebral Cavernous Malformations. Case Illustration. J Neurosurg. 2002;96(5):964. doi:10.3171/jns.2002.96.5.0964 - Pubmed